Grant: Project Grant

Living cells are divided into specialized compartments called organelles. Typically, membranes form a selective barrier between organelles and the cytoplasm, such that each compartment can maintain a distinct biochemical composition that is tailored to its function. By concentrating substrates and isolating reactions, membrane-bound organelles increase the rate and efficiency of cellular metabolism. However, cells also contain organelles that are not enclosed by membranes. With no physical barrier, molecules can freely exchange between these compartments and the surrounding cytoplasm or nucleoplasm. Recent progress has focused on the composition and assembly of membraneless organelles, but their function remains poorly understood. The proposed research aims to establish how the unusual structure of membraneless organelles impacts their function. To answer this question, we will use quantitative imaging to visualize the nucleolus in the model organism C. elegans. The nucleolus is a membraneless organelle that produces ribosomes, molecular machines that a cell needs to grow. Indeed, cancer cells, which experience uncontrolled growth, have enlarged and hyperactive nucleoli. Moreover, there is increasing evidence that links neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and Huntington's disease, to changes in the fluidity and activity of stress granules and other membraneless organelles. Thus, understanding the relationship between the fluidity and activity of the nucleolus in the worm has the potential to advance the diagnosis, treatment and prevention of human disease.